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Antiproliferative effects of LY-2183240 combined with various chemotherapeutic drugs in an isobolographic in vitro model of malignant melanoma. | LitMetric

AI Article Synopsis

  • Recent advances in melanoma treatment have been hindered by the high cost and side effects of new therapies, highlighting the need for more affordable and effective options.
  • This study investigated LY-2183240, which inhibits anandamide reuptake and fatty acid amide hydrolase, for its potential antiproliferative and cytotoxic effects on various melanoma cell lines.
  • Results showed that LY-2183240 combined well with docetaxel, paclitaxel, and mitoxantrone, indicating it could be a useful additive treatment, but not with cisplatin due to antagonistic interactions.

Article Abstract

Despite a great progress in identifying treatment options for patients with malignant melanoma, novel therapies tend to be costly and, in some cases, produce adverse effects forcing the melanoma patients to withdraw drugs. There is a strong need for less expensive drugs with a more favorable spectrum of anticancer actions. This study was designed to assess whether LY-2183240 (a potent inhibitor of both, anandamide cellular reuptake and fatty acid amide hydrolase (FAAH), an enzyme that degrades anandamide) has antiproliferative and cytotoxic effects on various human malignant melanoma cell lines (primary A375 and FM55P, metastatic SK-MEL28 and FM55M2) when administered alone or in combination with docetaxel, paclitaxel, mitoxantrone and cisplatin via the MTT assay. The MTT, LDH and BrdU assays were used to evaluate the potency and safety of LY-2183240, whereas isobolographic analysis of interactions was applied to characterize the interactions of LY-2183240 with the studied chemotherapeutics (docetaxel, paclitaxel, mitoxantrone and cisplatin). The isobolography confirmed that the combinations of LY-2183240 with docetaxel, paclitaxel and mitoxantrone produced additive interactions in all the tested melanoma cell lines. Only two antagonistic interactions for LY-2183240 combined with cisplatin in the A375 and FM55P cell lines were observed by the MTT assay. In conclusion, LY-2183240 can be considered an add-on drug for the treatment of melanoma, when combined with docetaxel, paclitaxel, or mitoxantrone, but not with cisplatin.

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Source
http://dx.doi.org/10.1016/j.ejphar.2024.176937DOI Listing

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